Effectiveness of teriflunomide on No Evidence of Disease Activity and cognition in relapsing remitting multiple sclerosis: results of the NEDA3PLUS study.
Cognition
Multiple sclerosis
No Evidence of Disease Activity
Observational
Teriflunomide
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
received:
19
04
2023
accepted:
11
06
2023
revised:
08
06
2023
medline:
21
9
2023
pubmed:
5
7
2023
entrez:
5
7
2023
Statut:
ppublish
Résumé
Cognitive impairment (CI) is a prevalent and debilitating manifestation of multiple sclerosis (MS); however, it is not included in the widely used concept of No Evidence of Disease Activity (NEDA-3). We expanded the NEDA-3 concept to NEDA-3 + by encompassing CI assessed through the Symbol Digit Modality Test (SDMT) and evaluated the effect of teriflunomide on NEDA3 + in patients treated in a real-world setting. The value of NEDA-3 + in predicting disability progression was also assessed. This 96-weeks observational study enrolled patients already on treatment with teriflunomide for ≥ 24 weeks. The predictiveness of NEDA-3 and NEDA-3 + at 48 weeks on the change in motor disability at 96 weeks was compared through a two-sided McNemar test. The full analysis set (n = 128; 38% treatment naïve) featured relatively low level of disability (baseline EDSS = 1.97 ± 1.33). NEDA-3 and NEDA-3 + statuses were achieved by 82.8% and 64.8% of patients, respectively at 48 weeks vs. baseline, and by 57.0% and 49.2% of patients, respectively at 96 weeks vs. baseline. All patients except one were free of disability progression at Week 96, and NEDA-3 and NEDA-3 + were equally predictive. Most patients were free of relapse (87.5%), disability progression (94.5%) and new MRI activity (67.2%) comparing 96 weeks with baseline. SDMT scores were stable in patients with baseline score ˃35 and improved significantly in those with baseline score ≤ 35. Treatment persistence was high (81.0% at Week 96). Teriflunomide confirmed its real-world efficacy and was found to have a potentially beneficial effect on cognition.
Sections du résumé
BACKGROUND
BACKGROUND
Cognitive impairment (CI) is a prevalent and debilitating manifestation of multiple sclerosis (MS); however, it is not included in the widely used concept of No Evidence of Disease Activity (NEDA-3). We expanded the NEDA-3 concept to NEDA-3 + by encompassing CI assessed through the Symbol Digit Modality Test (SDMT) and evaluated the effect of teriflunomide on NEDA3 + in patients treated in a real-world setting. The value of NEDA-3 + in predicting disability progression was also assessed.
METHODS
METHODS
This 96-weeks observational study enrolled patients already on treatment with teriflunomide for ≥ 24 weeks. The predictiveness of NEDA-3 and NEDA-3 + at 48 weeks on the change in motor disability at 96 weeks was compared through a two-sided McNemar test.
RESULTS
RESULTS
The full analysis set (n = 128; 38% treatment naïve) featured relatively low level of disability (baseline EDSS = 1.97 ± 1.33). NEDA-3 and NEDA-3 + statuses were achieved by 82.8% and 64.8% of patients, respectively at 48 weeks vs. baseline, and by 57.0% and 49.2% of patients, respectively at 96 weeks vs. baseline. All patients except one were free of disability progression at Week 96, and NEDA-3 and NEDA-3 + were equally predictive. Most patients were free of relapse (87.5%), disability progression (94.5%) and new MRI activity (67.2%) comparing 96 weeks with baseline. SDMT scores were stable in patients with baseline score ˃35 and improved significantly in those with baseline score ≤ 35. Treatment persistence was high (81.0% at Week 96).
CONCLUSION
CONCLUSIONS
Teriflunomide confirmed its real-world efficacy and was found to have a potentially beneficial effect on cognition.
Identifiants
pubmed: 37405689
doi: 10.1007/s00415-023-11820-0
pii: 10.1007/s00415-023-11820-0
pmc: PMC10511573
doi:
Substances chimiques
teriflunomide
1C058IKG3B
Types de publication
Observational Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4687-4696Informations de copyright
© 2023. The Author(s).
Références
Multiple Sclerosis International Federation (2020) Atlas of MS 3rd edition. Mult Scler Int Fed. 1–37
Markowitz CE (2013) Multiple sclerosis update. Am J Manag Care 19(16):S294–S300
pubmed: 24494618
Bar-Or A, Pachner A, Menguy-Vacheron F et al (2014) Teriflunomide and its mechanism of action in multiple sclerosis. Drugs 74(6):659–674
doi: 10.1007/s40265-014-0212-x
pubmed: 24740824
pmcid: 4003395
Miller AE (2021) An updated review of teriflunomide’s use in multiple sclerosis. Neurodegener Dis Manag 11(5):387–409
doi: 10.2217/nmt-2021-0014
pubmed: 34486382
Confavreux C, O’Connor P, Comi G et al (2014) Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol 13(3):247–256
doi: 10.1016/S1474-4422(13)70308-9
pubmed: 24461574
O’Connor P, Wolinsky JS, Confavreux C et al (2011) Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med 365(14):1293–1303
doi: 10.1056/NEJMoa1014656
pubmed: 21991951
Vermersch P, Czlonkowska A, Grimaldi LME et al (2014) Teriflunomide versus subcutaneous interferon β-1a in patients with relapsing multiple sclerosis: a randomised, controlled phase 3 trial. Mult Scler 20(6):705–716
doi: 10.1177/1352458513507821
pubmed: 24126064
O’Connor P, Comi G, Freedman MS et al (2016) Long-term safety and efficacy of teriflunomide: nine-year follow-up of the randomized TEMSO study. Neurology 86(10):920–930
doi: 10.1212/WNL.0000000000002441
pubmed: 26865517
pmcid: 4782117
Miller AE, Olsson TP, Wolinsky JS et al (2020) Long-term safety and efficacy of teriflunomide in patients with relapsing multiple sclerosis: results from the TOWER extension study. Mult Scler Relat Disord. https://doi.org/10.1016/j.msard.2020.102438
doi: 10.1016/j.msard.2020.102438
pubmed: 33310418
pmcid: 7363561
Coyle PK, Khatri B, Edwards KR et al (2017) Patient-reported outcomes in relapsing forms of MS: Real-world, global treatment experience with teriflunomide from the Teri-PRO study. Multiple Scler Relat Disord 17:107–115
doi: 10.1016/j.msard.2017.07.006
Rotstein D, Solomon JM, Sormani MP et al (2022) Association of No Evidence of Disease Activity with no long-term disability progression in multiple sclerosis a systematic review and meta-analysis. Neurology 99(2):e209–e220
doi: 10.1212/WNL.0000000000200549
Giovannoni G, Arnold DL, Cohen JA et al (2012) Disease activity free status in CARE-MS I phase 3 study. http://www.slideshare.net/gavingiovannoni/disease-activity-free-status-on-alemtuzumab-vs-ifnbeta1a-carems-1-study . Accessed Aug 13, 2012
Giovannoni G, Cook S, Rammohan K et al (2011) Sustained disease-activity-free status in patients with relapsing–remitting multiple sclerosis treated with cladribine tablets in the CLARITY study: a post hoc and subgroup analysis. Lancet Neurol 10:329–337. https://doi.org/10.1016/S1474-4422(11)70023-0
doi: 10.1016/S1474-4422(11)70023-0
pubmed: 21397565
Havrdova E, Galetta S, Hutchinson M et al (2009) Effect of natalizumab on clinical and radiological disease activity in multiple sclerosis: a retrospective analysis of the natalizumab safety and efficacy in relapsing–remitting multiple sclerosis (AFFIRM) study. Lancet Neurol 8:254–260. https://doi.org/10.1016/S1474-4422(09)70021-3
doi: 10.1016/S1474-4422(09)70021-3
pubmed: 19201654
Havrdova E, Gold R, Fox RJ et al (2013) BG-12 (dimethyl fumarate) treatment for relapsing–remitting multiple sclerosis (RRMS) increases the proportion of patients free of measured clinical and neuroradiologic disease activity in the phase 3 studies. Neurology 80(Meeting Abstract 1):P07.106
Kappos L, Radue E, O’Connor P et al (2011) Fingolimod treatment increases the proportion of patients who are free from disease activity in multiple sclerosis: results from a phase 3, placebo-controlled study (FREEDOMS). Neurology 76(Suppl 4):A563
Khatri B, Barkhof F, Comi G et al (2012) Fingolimod treatment increases the proportion of patients who are free from disease activity in multiple sclerosis compared to IFN-b1a: results from a phase 3, active-controlled study (TRANSFORMS). Neurology 78(Meeting Abstract 1):PD5.006
Freedman M, O’Connor P, Wolinsky J et al (2012) Teriflunomide increases the proportion of patients free from disease activity in the TEMSO phase III study. Neurology 78(Meeting Abstract 1):PD5.007
Amato MP, Morra VB, Falautano M et al (2018) Cognitive assessment in multiple sclerosis—an Italian consensus. Neurol Sci 39:1317–1324
doi: 10.1007/s10072-018-3427-x
pubmed: 29766386
Meca-Lallana V, Gascón-Giménez F, Ginestal-López RC et al (2021) Cognitive impairment in multiple sclerosis: diagnosis and monitoring. Neurol Sci 42:5183–5193
doi: 10.1007/s10072-021-05165-7
pubmed: 33796947
pmcid: 8642331
Giovannoni G, Tomic D, Havrdovà E et al (2017) “No evident disease activity”: the use of combined assessments in the management of patients with multiple sclerosis. Mult Scler J 23(9):1179–1187
doi: 10.1177/1352458517703193
Lu G, Beadnall H, Wang C et al (2017) The prognostic utility of No Evidence of Disease Activity (NEDA). J Neurol Neurosurg Psychiatry 88:e1
doi: 10.1136/jnnp-2017-316074.13
Margoni M, Rinaldi F, Riccardi A et al (2020) No Evidence of Disease Activity including cognition (NEDA-3 plus) in naïve pediatric multiple sclerosis patients treated with natalizumab. J Neurol 267(1):100–105. https://doi.org/10.1007/s00415-019-09554-z . (Epub 2019 Sep 27)
doi: 10.1007/s00415-019-09554-z
pubmed: 31562558
Hartung HP, Holmoy H, Wuerfel J et al (2022) Ocrelizumab in patients with early-stage RRMS: results from the phase IIIb ENSEMBLE trial and the matched real-world NTD registry cohort. Presented at the 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS); Amsterdam, 26–28 October 2022
Goretti B, Niccolai C, Hakiki B et al (2014) The brief international cognitive assessment for multiple sclerosis (BICAMS): normative values with gender, age and education corrections in the Italian population. BMC Neurol 14:171. https://doi.org/10.1186/s12883-014-0171-6
doi: 10.1186/s12883-014-0171-6
pubmed: 25204350
pmcid: 4172942
Bucello S, Annovazzi P, Ragonese P et al (2021) Real world experience with teriflunomide in multiple sclerosis: the TER-Italy study. J Neurl 268:2922–2932
doi: 10.1007/s00415-021-10455-3
Lorefice L, Pilotto S, Fenu G et al (2022) Evolution of teriflunomide use in multiple sclerosis: a real-word experience. J Neurol Sci 438:120292
doi: 10.1016/j.jns.2022.120292
pubmed: 35605316
Zanghì A, Avolio C, Amato MP et al (2022) Real world comparison of teriflunomide and dimethyl fumarate in naïve relapsing multiple sclerosis patients: evidence from the Italian MS register. Mult Scler Relat Disord 58:103489. https://doi.org/10.1016/j.msard.2022.103489 . (Epub 2022 Jan 2)
doi: 10.1016/j.msard.2022.103489
pubmed: 35032879
Rotstein DL, Healy BC, Malik MT et al (2015) Evaluation of No Evidence of Disease Activity in a 7-year longitudinal multiple sclerosis cohort. JAMA Neurol 72(2):152–158
doi: 10.1001/jamaneurol.2014.3537
pubmed: 25531931
Hegen H, Bsteh G, Berger T (2018) ‟No evidence of disease activity”—is it an appropriate surrogate in multiple sclerosis? Eur J Neurol 25(9):1107-e101
doi: 10.1111/ene.13669
pubmed: 29687559
pmcid: 6099351
Gasperini C, Prosperini L, Tintoré M et al (2019) Unraveling treatment response in multiple sclerosis: a clinical and MRI challenge. Neurology 92(4):180–192
doi: 10.1212/WNL.0000000000006810
pubmed: 30587516
pmcid: 6345120
Cortese R, Carotenuto A, DiFilippo M et al (2021) Editorial: cognition in multiple sclerosis. Front Neurol. https://doi.org/10.3389/fneur.2021.751687 . (30 August 2021)
doi: 10.3389/fneur.2021.751687
pubmed: 34899579
pmcid: 8654928
Sumowski JF, Benedict R, Enzinger C (2018) Cognition in multiple sclerosis. Neurology 90(6):278–288
doi: 10.1212/WNL.0000000000004977
pubmed: 29343470
pmcid: 5818015